Quercetin inhibits LPS-induced macrophage migration by suppressing the iNOS/FAK/paxillin pathway and modulating the cytoskeleton

Cell Adh Migr. 2019 Dec;13(1):1-12. doi: 10.1080/19336918.2018.1486142. Epub 2018 Aug 1.

Abstract

The natural flavonoid quercetin has antioxidant, anti-inflammatory, and anticancer effects. We investigated the effect of quercetin on lipopolysaccharide (LPS)-induced macrophage migration. Quercetin significantly attenuated LPS-induced inducible nitric oxide synthase (iNOS)-derived nitric oxide (NO) production in RAW264.7 cells without affecting their viability. Additionally, quercetin altered the cell size and induced an elongated morphology and enlarged the vacuoles and concentrated nuclei. Quercetin significantly disrupted the F-actin cytoskeleton structure. Furthermore, quercetin strongly inhibited LPS-induced macrophage adhesion and migration in a dose-dependent manner. Moreover, quercetin inhibited the LPS-induced expression of p-FAK, p-paxillin, FAK, and paxillin as well as the cytoskeletal adapter proteins vinculin and Tensin-2. Therefore, quercetin suppresses LPS-induced migration by inhibiting NO production, disrupting the F-actin cytoskeleton, and suppressing the FAK-paxillin pathway. Quercetin may thus have potential as a therapeutic agent for chronic inflammatory diseases.

Keywords: Quercetin; iNOS/FAK-paxillin pathway; macrophage; migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / drug effects*
  • Actins / metabolism
  • Animals
  • Antioxidants / pharmacology
  • Cell Movement / drug effects
  • Cell Movement / physiology*
  • Focal Adhesion Kinase 1 / genetics
  • Focal Adhesion Kinase 1 / metabolism*
  • Gene Expression Regulation
  • Lipopolysaccharides / pharmacology*
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / physiology*
  • Mice
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism*
  • Paxillin / genetics
  • Paxillin / metabolism*
  • Quercetin / pharmacology*
  • RAW 264.7 Cells

Substances

  • Actins
  • Antioxidants
  • Lipopolysaccharides
  • Paxillin
  • Pxn protein, mouse
  • Quercetin
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Focal Adhesion Kinase 1
  • Ptk2 protein, mouse

Grants and funding

This work was supported by the National Natural Science Foundation of China [81703969]; Scientific Research Foundation of Jiangsu Province [BK20160480]; Scientific Research Foundation of Yangzhou [No. YZ2017074].